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TOPLINE:

Severe neonatal morbidity (SNM) significantly increased the risk for death from infancy through late adolescence, particularly for neurologic conditions. Female infants and those born term with SNM faced higher relative mortality risks.

METHODOLOGY:

• Researchers conducted a population-based cohort study using data from the Swedish Medical Birth Register to assess the association between SNM and all-cause and cause-specific mortality from infancy to adolescence.
• This study included 2,098,752 live-born singleton infants born between 2002 and 2021, of whom 49,225 (2.4%) were diagnosed with SNM (defined as respiratory infections or neurologic or procedural complications within 27 days of birth).
• Mortality was classified on the basis of age as infancy (28 days to 11 months), early childhood (1-4 years), later childhood (5-9 years), and adolescence (≥ 10 years).
• Primary outcomes were all-cause and cause-specific mortality from 28 days to a follow-up duration of 21.2 years.

TAKEAWAY:

• The mortality rate was 1.81 vs 0.13 per 1000 person-years among children with SNM vs those without SNM (adjusted hazard ratio [aHR], 5.92; 95% CI, 5.27-6.64). Neurologic morbidity had the strongest association (aHR, 17.67; 95% CI, 15.08-20.71).
• Female children with SNM had a higher risk for mortality than male children (aHR, 7.28 vs 4.97; P for interaction < .001), with the association between SNM and neurologic morbidity notably stronger among female children.
• Among children aged 1 year or older, SNM was strongly associated with deaths from neurologic diseases (aHR, 18.64; 95% CI, 12.51-27.79), circulatory diseases (aHR, 5.41; 95% CI, 2.67-10.94), and metabolic disorders (aHR, 3.56; 95% CI, 1.70-7.44).
• Among children with SNM, those born preterm had higher absolute mortality rates than those born term (2.76 vs 1.30 per 1000 person-years); however, infants born term showed a stronger relative risk than those born preterm (aHR, 7.16 vs 3.51).

IN PRACTICE:

"Efforts to further prevent severe neonatal morbidity, ensure early identification, and provide long-term follow-up care may help reduce mortality and inform discussions with families regarding prognosis and follow-up needs," the authors wrote.

SOURCE:

This study was led by Hillary Graham, MS, Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. It was published online on June 10, 2025, in JAMA Pediatrics.

LIMITATIONS:

This study included over 20 years of follow-up; mortality data became limited beyond 15 years. Lower early-life survival in the earliest birth cohort may have led to survivor bias, potentially underestimating the long-term risk for mortality. Although the sibling-controlled analysis helps address familial confounding, it may still be affected by unmeasured differences between siblings.

DISCLOSURES:

This study was supported by grants from the Swedish Research Council and Stockholm City Council, ALF Medicine. The authors reported having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.